More than a third of the population in the United States occasionally has heartburn, and about one-in-ten people have it daily. Infrequent heartburn does not usually have any serious consequences, but frequent heartburn (recurring more than twice per week) can result in severe side-effects. Early management is important to maintain one's health.
A working explanation of heartburn requires an understanding of the structure and action of the esophagus. The esophagus is a tube that connects one's throat to their stomach. The esophagus of an adult is about 10 in (25 cm) long, and it is lined with squamous (plate-like) epithelial cells, coated with mucus, and surrounded by muscles that push food to the stomach by sequential waves of contraction (peristalsis). The lower esophageal sphincter (LES) is a thick band of muscles that encircles the esophagus just above the uppermost part of the stomach. This sphincter is usually tightly closed and normally opens only when food passes from the esophagus into the stomach. Thus, the contents of the stomach are normally kept from moving back into the esophagus. An exception to this is when one burps, the LES opens potentially enabling acid reflux.
The stomach has a thick mucus coating that protects it from the strong acid that is secreted into the interior of the stomach when food is present. The much thinner esophageal coating doesn't provide protection against acid. Thus, if the LES opens inappropriately or fails to close completely, potentially some stomach contents could leak into the esophagus, where the acid can burn the esophagus. The resulting burning sensation is called heartburn.
Occasional heartburn has no serious long-lasting effects, but repeated episodes of gastroesophageal reflux can ultimately lead to esophageal inflammation (esophagitis) and other damage. If episodes occur more frequently than twice a week, and the esophagus is repeatedly subjected to acid and digestive enzymes from the stomach, ulcerations, scarring, and thickening of the esophagus walls can result. This thickening of the esophagus wall causes a narrowing of the interior of the esophagus. The narrowing affects swallowing and peristaltic movements. Repeated irritation can also result in changes in the types of cells that line the esophagus. The condition associated with these changes is termed Barrett's syndrome and can lead to esophageal cancer.
A number of different factors may contribute to LES malfunction with its consequent gastroesophageal acid reflux. They include: eating large meals that distend the stomach causing the LES to open. Lying down within two to three hours of eating can cause the LES to open. Obesity, pregnancy, and tight clothing can impair the ability of the LES to stay closed by putting pressure on the abdomen. Certain drugs, notably nicotine, alcohol, diazepam (Valium), meperidine (Demerol), theophylline, morphine, prostaglandins, calcium channel blockers, nitrate heart medications, anticholinergic and adrenergic drugs (drugs that limit nerve reactions), including dopamine, can relax the LES. Progesterone is thought to relax the LES. Even greasy foods and some other foods such as chocolate, coffee, and peppermint have been reported to relax the LES. Paralysis and systemic scleroderma can cause the LES to malfunction. Hiatus hernia may also cause heartburn according to some gastroenterologists. Hiatus hernia is a protrusion of part of the stomach through the diaphragm to a position next to the esophagus.
Heartburn itself is a symptom. Other symptoms also caused by gastroesophageal reflux can be associated with heartburn. Often heartburn sufferers can salivate excessively or can regurgitate (burp) stomach contents into their mouths, leaving a sour or bitter taste. Frequent gastroesophageal reflux leads to additional complications including difficult or painful swallowing, sore throat, hoarseness, coughing, laryngitis, wheezing, asthma, pneumonia, gingivitis, halitosis and earache.
The literature reports that occasional heartburn is commonly treated with over-the-counter antacids. These products go straight to the esophagus and immediately begin to decrease acidity. However, they should not be used as the sole treatment for heartburn sufferers who either have two or more episodes per week or who suffer for periods of more than three weeks. There is a risk of kidney damage and other metabolic changes.
H2 blockers are acid reducers for Gastroesophageal Reflux Disease (GERD). Chemically, they are histamine receptor blockers which inhibit the formation of stomach acid, and mechanistically they are relatively slow acting. Examples include famotidine in Pepsid AC™ which is a product of McNeil Consumer Pharmaceuticals Co., ranitidine in Zantac™ which is a product of Boehringer Ingelheim Pharmaceuticals, Inc, cimetidine in Tagamet™ which is a product of Prestige Brands, Inc, and nizatidine in Axid™ which was developed by Eli Lilly. The IUPAC name for famotidine is 3-([2-(diaminomethyleneamino)thiazol-4-yl]methylthio)-N′-sulfamoyl-propanimid-amide. The IUPAC name for cimetidine is 2-cyano-1-methyl-3-(2-[(5-methyl-1H-imidazol-4-yl)-methylthio]ethyl) guanidine. Famotidine is reputed to be 30 times more active than cimetidine. In Famotidine, the imidazole-ring of cimetidine is replaced with a 2-guanidinothiazole ring. Clinically, famotidine has been found to be 30 times more active than cimetidine. The IUPAC name for ranitidine is N-(2-[(5-[(dimethylamino) methyl]furan-2-yl) methylthio]ethyl)-N′-methyl-2-nitroethene-1,1-diamine. It should be noted that ranitidine is also known to give false positives for methamphetamine on drug tests. The IUPAC name for nizatidine is N-(2-[(2-[(dimethylamino)methyl]thiazol-4-yl)methylthio]ethyl)-N-methyl-2-nitroethene-1,1-diamine.
Ranitidine is reported to decrease mucosal perfusion in patients with acute renal or cardiac failure, and increases their risk of death. Fungal sepsis has been observed in some patients on ranitidine. All drugs in its class decrease gastric intrinsic factor secretion, which can significantly reduce absorption of protein-bound vitamin B12 in humans. Elderly patients taking H2 receptor antagonists are more likely to require B12 supplementation than those not taking such drugs. H2 blockers may also reduce the absorption of drugs (azole antifungals, calcium carbonate) that require an acidic stomach. By suppressing acid-mediated breakdown of proteins, antacid preparations such as ranitidine may lead to an elevated risk of developing food or drug allergies, due to undigested proteins, which can then pass into the gastrointestinal tract, wherein sensitization occurs. Whether this risk occurs with only long-term use or with short-term use, as well, is unclear. Ranitidine and other histamine H2 receptor antagonists may increase the risk of pneumonia in hospitalized patients. They may also increase the risk of community-acquired pneumonia in adults and children. Multiple studies suggest that the use of H2 receptor antagonists, such as ranitidine, may increase the risk of infectious diarrhea, including traveler's diarrhea and salmonellosis.
In general, H2 antagonists increase the risk of developing food allergies. Patients who take these agents develop higher levels of Immunoglobulin E (IgE). IgE is a class of antibody found in mammals that provides important immune defense. IgE also plays an essential role in type I hypersensitivity, which manifests various allergic diseases, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergy, and some types of chronic urticaria and atopic dermatitis. IgE also plays a pivotal role in allergic conditions, such as anaphylactic reactions to certain drugs, bee stings, and antigen preparations used in specific desensitization immunotherapy.
H2 blockers are usually effective at preventing heartburn, but not stopping an ongoing episode. H2 blocker treatment also allows healing of esophageal damage, but is not very effective when there is a high degree of damage. It takes 30-45 minutes for these drugs to take effect, so they must be taken prior to an episode. Thus, they should be taken daily, usually two to four times per day for several weeks. Six to 12 weeks of standard-dose treatment relieves symptoms in about one-half the patients. Higher doses relieve symptoms in a greater fraction of the population, but at least 25% of heartburn sufferers are not helped by H2 blockers.
LES is reportedly lessened with prokinetic agents (also known as motility drugs), stimulating it to close more tightly, thereby retaining the stomach contents out of the esophagus. Typically, prokinetic agents can also stimulate contractions of the colon, and an argument could be made that prokinetic agents are largely laxatives.
Proton Pump Inhibitors (PPIs) are the newest class of drugs to reduce heartburn, GERD and acid reflux. The stomach wall has cells that pump acid into the stomach. The reported mechanism is that the PPI binds irreversibly to a hydrogen/potassium ATPase enzyme (i.e. proton pump) on gastric parietal cells, which blocks the secretion of hydrogen ions; where the protons combine with chloride ions in the stomach lumen to form gastric acid. Proton Pump Inhibitors include: Aciphex™ (raberprazole) is a product of Eisai Inc, Nexium™ (esomeprazole) is a product of AstraZeneca, Prevacid™ (lansoprazole) is a product of Novartis, Prilosec™ (omeprazole) is a product of Proctor and Gamble, and Protonix™ (pantoprazole) is a product of Pfizer. With many PPI's very serious interactions can occur with alcohol, and the most common side effect includes headache, and diarrhea.
The latest concern is that long term use of PPIs is increased bone fractures, low vitamin B12, and low magnesium levels. Furthermore, PPIs might increase the risk for dementia. Britta Haenisch and colleagues at the German Center for Neurodegenerative Diseases in Bonn studied 73,679 people ages 75 and older. The researchers found regular PPI users had at least a 44 percent increased risk of dementia compared with those not using the drugs.
Antacids that mechanistically work by reacting with stomach gastric acid, which contains hydrochloric acid (HCL), can potentially produce a gas, for example carbon dioxide. It has been speculated that the gas causes foaming within the stomach, and the bubbles then convey gastric acid past the LES into the esophagus. The pH of the stomach gastric acid is 1.5 to 3.5 (around 0.5%, or 5000 parts per million). The acid plays a key role in digestion of proteins, by activating digestive enzymes, and making ingested proteins unravel so that digestive enzymes break down the long chains of amino acids. The hydrochloric acid is at a relatively low acid concentration, and the acid functions more catalytically than reactively. Reputedly, there are some cells in the stomach that produce bicarbonate, a base, to buffer the fluid, ensuring that it does not become too acidic, so the stomach is capable of handling carbonate and bicarbonate without heart burn.